Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a mAb conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is a surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor types. Meanwhile, CD25-targeted NIR-PIT has been reported to achieve selective and local depletion of FOXP3+CD25+CD4+ regulatory T cells (Treg), which are primary immunosuppressive cells in the tumor microenvironment (TME), resulting in activation of local antitumor immunity. Combined NIR-PIT with CD44- and CD25-targeted agents has the potential to directly eliminate tumor cells and also amplify the immune response by removing FOXP3+CD25+CD4+ Tregs from the TME. We investigated the difference in therapeutic effects of CD44-targeted NIR-PIT alone, CD25-targeted NIR-PIT alone, and the combination of CD44- and CD25-targeted NIR-PIT in several syngeneic tumor models, including MC38-luc, LL/2, and MOC1. The combined NIR-PIT showed significant tumor growth inhibition and prolonged survival compared with CD44-targeted NIR-PIT alone in all tumor models and showed prolonged survival compared with CD25-targeted NIR-PIT alone in MC38-luc and LL/2 tumors. Combined CD44- and CD25-targeted NIR-PIT also resulted in some complete remissions. Therefore, combined NIR-PIT simultaneously targeting cancer antigens and immunosuppressive cells in the TME may be more effective than either type of NIR-PIT alone and may have potential to induce prolonged immune responses in treated tumors.

中文翻译：

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联合 CD44 和 CD25 靶向近红外光免疫疗法选择性杀死同基因小鼠癌症模型中的癌症和调节性 T 细胞。

近红外光免疫疗法 (NIR-PIT) 是一种新开发的选择性癌症治疗方法，可诱导坏死和免疫原性细胞死亡，并利用与光吸收染料 IR700DX 结合的单克隆抗体，由近红外光激活。尽管 CD44 是与耐药性相关的表面癌症标志物，但抗 CD44-IR700 NIR-PIT 会导致多种肿瘤类型的细胞生长受到抑制并延长存活时间。同时，据报道，靶向 CD25 的 NIR-PIT 可实现选择性和局部消耗 FOXP3+CD25+CD4+ 调节性 T 细胞 (Treg)，它们是肿瘤微环境 (TME) 中的主要免疫抑制细胞，从而激活局部抗肿瘤免疫. NIR-PIT 与 CD44 和 CD25 靶向药物相结合，有可能直接消除肿瘤细胞，并通过从 TME 中去除 FOXP3+CD25+CD4+ Treg 来增强免疫反应。我们研究了单独 CD44 靶向 NIR-PIT、单独 CD25 靶向 NIR-PIT 以及 CD44 和 CD25 靶向 NIR-PIT 组合在几种同源肿瘤模型（包括 MC38-luc、LL/ 2、MOC1。在所有肿瘤模型中，联合 NIR-PIT 与单独靶向 CD44 的 NIR-PIT 相比显示出显着的肿瘤生长抑制和延长的生存期，并且与单独靶向 CD25 的 NIR-PIT 在 MC38-luc 和 LL/2 肿瘤中显示出延长的生存期。结合 CD44 和 CD25 靶向 NIR-PIT 也导致一些完全缓解。所以，